Serum Sphingolipids Aid in Diagnosing Adult HIV-Negative Patients with Pulmonary Cryptococcosis: A Clinical Cohort Study

<bold>Background:</bold> Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in HIV-negative populations. However, the current antifungal drugs are insufficient, which cannot meet clinical needs <bold>Methods:</bold> Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. Meanwhile, we measured the antibacterial activity of SPLs. <bold>Results:</bold> The serum ceramide (Cer (d18:1/18:0)) level showed a significant increase in PC patients compared to controls and PA and TB patients (P < 0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. In addition, the minimal inhibitory concentration (MIC) of Cer (d18:1/18:0) against Cryptococcus neoformans (C. neoformans) H99 was 8 μg/ml, and the minimum fungicidal concentration (MFC) was 32 μg/ml. Time-killing curves of H99 showed that 4 MIC of Cer (d18:1/18:0) had fungicide activity. Subsequently, transmission electron microscopy (TEM) observations showed that Cer (d18:1/18:0) clearly breached the cell membrane and organelles of H99. <bold>Conclusions:</bold> We reported the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients. Cer (d18:1/18:0) exhibits strong anti-C. neoformans activity in vitro, mainly by destroying the permeability and related functions of Cryptococcus cell membranes.